Natural Killer (NK) cells are thought to play a role in the control of viral infection before the establishment of a specific cytolytic T cell response mediated by CD3-positive MHC-restricted T cells. Recently, specific recognition of alloantigens by NK cells was reported. Most of the cells displaying NK activity belong to the CD3-CD16+CD56+ subset of peripheral blood lymphocytes. The mechanism of target cell recognition by NK cells is still unknown. The aim of this study was (i) to determine whether target cell elements control the recognition and lysis by NK cells, and (ii) to purify a surface molecule from NK cells in sufficient amount to obtain amino-acid sequences. As a first step, it was established that NK clones from a normal individual were able to specifically recognize and kill normal cells from the same individual that had been infected in vitro with human Herpesvirus-6 (HHV-6). The results showed for the first time that specificity in target cell recognition by NK cells is controlled at several levels: first, at the level of the NK clone itself, and second, by genetically variable elements on the target cells that restrict recognition by NK cells. By use of a monoclonal antibody, a NK cell surface protein that is involved in target cell recognition was purified and partial amino-acid sequences were obtained. The ultimate goal of this project is to obtain molecular clones for this molecule and to define its role in target cell recognition.